ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.

Objective: Whether dissociation and depression are distinct constructs remains controversial. The aim of this study was to explore the interrelations and associated factors between them. Methods: This study included inpatients with major depressive disorder (MDD) and bipolar disorder with major depressive episode (BD). Clinical rating scales were used to measure levels of depression, dissociation, and psychotic symptoms. Generalized estimating equations were used to estimate interrelations between dissociation and related factors over time, including depression. Moreover, the impacts of individual items of the Hamilton Depression Rating Scale (HAMD) on dissociation were evaluated after multiple adjustments. Results: A total of 91 participants were included into the analysis, of whom 59 had MDD and 32 had BD. After standardized treatment, levels of depression and psychotic symptoms significantly decreased, whereas the level of dissociation did not. However, the level of dissociation significantly decreased in the high-dissociation group, and this was positively associated with the change in depression and psychotic symptoms. Female sex and comorbidity with borderline personality disorder were also positively correlated with dissociation. Among items of the HAMD, insomnia and gastrointestinal symptoms contributed to the association between depression and dissociation. Conclusion We identified a decoupled but intertwined relationship between dissociation and depression. Clinicians should be aware of this comorbidity and provide timely interventions for dissociation during clinical practice.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Objective: To systematically review the effect of physical activity (PA) on health related quality of life (HRQoL) among children and adolescents and the magnitude of association, so as to provide an evidence based support for optimizing health promotion strategies for children and adolescents. Methods: Medline (PubMed), EMBASE, the Cochrane Library, SCIELO, PEDro, CNKI, Wanfang and VIP databases were searched to collect literature on PA and HRQoL in children and adolescents, which were published up to January 1, 2025. Cochrane ROB tool and specific evaluation system were used to assess literature quality, Stata 16.0 software was used for Meta analysis. For descriptive studies, correlation( r ) and 95% confidence interval( CI ) were used as effect indicators, and the inverse variance method was used to merge the data. Standardized mean difference( SMD ) and 95% CI were used to calculate the combined effect size of intervention studies. Results: A total of 22 studies involving 27 303 healthy children and adolescents were included, including 9 descriptive studies and 13 intervention studies. The results of descriptive analysis showed that PA level was positively correlated with HRQoL ( r =0.27, 95% CI =0.21-0.32, P <0.01). The analysis of intervention studies showed that PA had significant effects on overall HRQoL ( SMD =0.10, 95% CI =0.05-0.16), physical functioning ( SMD =0.16, 95% CI =0.08-0.23), and mental functioning ( SMD =0.17, 95% CI =0.10-0.25)( P <0.01). Subgroup analysis found that the effects of physical activity on overall HRQoL, physiological function, and psychological function in children and adolescents were maximized when the intervention duration was less than 6 months ( SMD =0.13, 0.18, 0.20), the frequency was≥5 times per week ( SMD =0.13, 0.19, 0.24) and there was a supplementary plan( SMD =0.10, 0.18, 0.23)( P <0.01). Conclusion PA is an important factor affecting the HRQoL of healthy children and adolescents, and the systematic PA intervention has a effect on improving the HRQoL.

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.

Objective: Whether dissociation and depression are distinct constructs remains controversial. The aim of this study was to explore the interrelations and associated factors between them. Methods: This study included inpatients with major depressive disorder (MDD) and bipolar disorder with major depressive episode (BD). Clinical rating scales were used to measure levels of depression, dissociation, and psychotic symptoms. Generalized estimating equations were used to estimate interrelations between dissociation and related factors over time, including depression. Moreover, the impacts of individual items of the Hamilton Depression Rating Scale (HAMD) on dissociation were evaluated after multiple adjustments. Results: A total of 91 participants were included into the analysis, of whom 59 had MDD and 32 had BD. After standardized treatment, levels of depression and psychotic symptoms significantly decreased, whereas the level of dissociation did not. However, the level of dissociation significantly decreased in the high-dissociation group, and this was positively associated with the change in depression and psychotic symptoms. Female sex and comorbidity with borderline personality disorder were also positively correlated with dissociation. Among items of the HAMD, insomnia and gastrointestinal symptoms contributed to the association between depression and dissociation. Conclusion We identified a decoupled but intertwined relationship between dissociation and depression. Clinicians should be aware of this comorbidity and provide timely interventions for dissociation during clinical practice.

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*